Dyslipidemia paradox: Analysis from the veterans exercise testing study

Dyslipidemia is a well-established cardiovascular disease (CVD) risk factor, although its association with mortality is less clear. This study aimed to assess the association between established dyslipidemia criteria [National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel (ATP) III] and all-cause mortality in men.

Prospective cohort study of 1,479 men aged 59.7±10.7 years was conducted between 1987 and 2012. At baseline, dyslipidemia markers of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were assessed as an exposure. Cox proportional hazard models were analyzed adjusting for conventional health risk factors using all-cause mortality as an outcome.

Mean and standard deviations of TC, LDL-C and HDL-C were 199.5±45.2, 149.4±47.4 and 44.3±12.2 mg/dL, respectively. During 8.9±4.5 years follow-up, 284 participants died. Compared to TC <200 mg/dL, levels of 200-239 mg/dL and ≥240 mg/dL were associated with 13% [hazard ratio (HR) = 0.87, 95% confidence intervals (CI) (0.66-1.1)] and 37% [HR = 0.63, 95% CI (0.44-0.92)] lower risks of mortality (p trend = 0.048), respectively. Compared to LDL-C <130 mg/dL, levels of 130-189 mg/dL and ≥190 mg/dL were associated with 26% [HR = 0.74, 95% CI (0.57-0.97)] and 32% [HR = 0.68, 95% CI (0.48-0.98)] lower risks of mortality (p trend = 0.044), respectively. Mean survival time was 0.9 to 1.9 years longer with higher TC and LDL-C categories (both p = 0.001). HDL-C was not associated with mortality.

In reference to established dyslipidemia criteria, this study showed that higher TC and LDL-C were independently and paradoxically associated with lower risk of all-cause mortality and longer survival time in men. Along with previous reports, these novel findings support a rigorous reevaluation of evidence on dyslipidemia and health risks. Systematic review and meta-analysis are warranted for evidence-based recommendations on dyslipidemia for primary and secondary prevention of CVD.